IL-24→dihydroceramide→Tumor Suppressor Protein p53→NF-kappa B→NF-kappa B→poly-ADP-ribose

• 18281515(IL-24): Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells.

  Melanoma differentiation-associated gene-7 / interleukin-24 (mda-7 / IL-24) is a novel cytokine displaying selective apoptosis-inducing activity in transformed cells without harming normal cells.

• 20103619(dihydroceramide): PERK-dependent regulation of ceramide synthase 6 and thioredoxin play a key role in mda-7/IL-24-induced killing of primary human glioblastoma multiforme cells.

  Melanoma differentiation associated gene-7 (mda-7) encodes IL-24 , a cytokine that can selectively trigger apoptosis in transformed cells.

• 12606943(Tumor Suppressor Protein p53): Melanoma differentiation associated gene-7, mda-7/IL-24, selectively induces growth suppression, apoptosis and radiosensitization in malignant gliomas in a p53-independent manner.

  We presently demonstrate that Ad.mda-7 induces growth inhibition and apoptosis in malignant human gliomas expressing both mutant and wild-type p53 , and these effects correlate with an elevation in expression of members of the growth arrest and DNA damage (GADD) gene family.

• 15383566(NF-kappa B): Melanoma differentiation-associated gene-7/IL-24 gene enhances NF-kappa B activation and suppresses apoptosis induced by TNF.

  However , TNF-induced NF-kappaB activation was significantly enhanced in mda-7-transfected cells , as indicated by DNA binding , p65 translocation , and NF-kappaB-dependent reporter gene expression.

• 11577079(NF-kappa B): The sequence-specific DNA binding of NF-kappa B is reversibly regulated by the automodification reaction of poly (ADP-ribose) polymerase 1.

  Recent studies suggest that the synthesis of protein-bound ADP-ribose polymers catalyzed by poly (ADP-ribose) polymerase-1 (PARP-1) regulates eucaryotic gene expression , including the NF-kappaB-dependent pathway.

• 6325408(poly-ADP-ribose): Poly (ADP-Ribose) synthetase. Separation and identification of three proteolytic fragments as the substrate-binding domain, the DNA-binding domain, and the automodification domain.

  These results indicate that poly (ADP-ribose) synthetase contains three separable domains , the first possessing the site for binding of the substrate , NAD , the second containing the site for binding of DNA , and the third acting as the site (s) for accepting poly (ADP-ribose).